Spatially resolved RNA-sequencing of the embryonic heart identifies a role for Wnt/β-catenin signaling in autonomic control of heart rate

Elife. 2018 Feb 5:7:e31515. doi: 10.7554/eLife.31515.


Development of specialized cells and structures in the heart is regulated by spatially -restricted molecular pathways. Disruptions in these pathways can cause severe congenital cardiac malformations or functional defects. To better understand these pathways and how they regulate cardiac development we used tomo-seq, combining high-throughput RNA-sequencing with tissue-sectioning, to establish a genome-wide expression dataset with high spatial resolution for the developing zebrafish heart. Analysis of the dataset revealed over 1100 genes differentially expressed in sub-compartments. Pacemaker cells in the sinoatrial region induce heart contractions, but little is known about the mechanisms underlying their development. Using our transcriptome map, we identified spatially restricted Wnt/β-catenin signaling activity in pacemaker cells, which was controlled by Islet-1 activity. Moreover, Wnt/β-catenin signaling controls heart rate by regulating pacemaker cellular response to parasympathetic stimuli. Thus, this high-resolution transcriptome map incorporating all cell types in the embryonic heart can expose spatially restricted molecular pathways critical for specific cardiac functions.

Keywords: Islet-1; RNA-seq; developmental biology; heart; pacemaker; stem cells; wnt; zebrafish.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Heart / embryology*
  • Heart / physiology*
  • Heart Rate*
  • High-Throughput Nucleotide Sequencing
  • Spatio-Temporal Analysis
  • Wnt Signaling Pathway*
  • Zebrafish
  • Zebrafish Proteins / metabolism*
  • beta Catenin / metabolism*


  • Zebrafish Proteins
  • beta Catenin
  • ctnnb1 protein, zebrafish

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